Dimensional Priming Reprograms Adipose-Derived Stromal Cells to Promote Pancreatic Cancer Progression.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background The tumor microenvironment (TME) plays a central role in pancreatic ductal adenocarcinoma (PDAC) progression, yet how mechanical cues shape stromal cell behavior remains poorly defined. Here, we investigate how dimensional priming of adipose-derived stromal cells (ADSCs) alters their immunomodulatory functions and subsequent impact on PDAC growth. Methods ADSCs were cultured under two-dimensional (2D) or three-dimensional (3D) conditions and evaluated using in vitro co-culture systems with PDAC organoids and in vivo xenograft models. Stromal phenotype, cytokine secretion, tumor growth, invasion, and immune cell infiltration were assessed. Results ADSCs cultured in three-dimensional (3D) hydrogels exhibited reduced Caveolin-1 (CAV-1) expression and reprogramming toward a stress-adapted, CAF-like phenotype compared with two-dimensional (2D) cultures. In vitro, 2D-primed ADSCs constrained PDAC organoid growth, increased MMP-2 activity, and required direct cell-cell contact to suppress tumor viability. By contrast, 3D-primed ADSCs preserved organoid structure but markedly enhanced tumor cell migration through soluble factors, accompanied by increased IL-6 and TNF-α and reduced IL-10 secretion during co-culture. In vivo, 3D-primed ADSCs promoted the largest tumors with aggressive invasion and loss of Col-Tgel containment associated with tumor expansion, whereas 2D-primed

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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